ArticleTranslational psychiatry2015
A molecular model for neurodevelopmental disorders.
Article in Translational psychiatry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 41 citations in OpenAlex.
- Benzo[a]pyrene-induced AHR activation in human ESCs primes premature neurogenesis in cerebral organoids.Journal of hazardous materials · 2026Article
- Benzo[a]pyrene-induced AHR activation in human ESCs primes premature neurogenesis in brain organoids.bioRxiv : the preprint server for biology · 2026Article
- 5-mC DNA methylation in neurodevelopment: from molecular mechanisms to therapeutic implications.Molecular biology reports · 2025Review
- Master regulators of neurogenesis: the dynamic roles of Ephrin receptors across diverse cellular niches.Translational psychiatry · 2024Review
- Transcriptional Dysregulation and Impaired Neuronal Activity inInternational journal of molecular sciences · 2023Article
- Transcriptome analysis of MBD5-associated neurodevelopmental disorder (MAND) neural progenitor cells reveals dysregulation of autism-associated genes.Scientific reports · 2021Article
- TheeLife · 2021Article
- Exposure to bisphenol A differentially impacts neurodevelopment and behavior in Drosophila melanogaster from distinct genetic backgrounds.Neurotoxicology · 2021Article
- Chromatin Imbalance as the Vertex Between Fetal Valproate Syndrome and Chromatinopathies.Frontiers in cell and developmental biology · 2021Review
- Transcriptional signatures of participant-derived neural progenitor cells and neurons implicate altered Wnt signaling in Phelan-McDermid syndrome and autism.Molecular autism · 2020Article
- Transcriptional consequences of MBD5 disruption in mouse brain and CRISPR-derived neurons.Molecular autism · 2020Article
- Identification of Molecular Signatures in Neural Differentiation and Neurological Diseases Using Digital Color-Coded Molecular Barcoding.Stem cells international · 2020Review
- A novel MBD5 mutation in an intellectually disabled adult female patient with epilepsy: Suggestive of early onset dementia?Molecular genetics & genomic medicine · 2019Article
- Induced Pluripotent Stem Cells; New Tools for Investigating Molecular Mechanisms in Anorexia Nervosa.Frontiers in nutrition · 2019Review
- Patient-Derived Stem Cells, AnotherFrontiers in pediatrics · 2019Review
- Brain-enriched microRNAs circulating in plasma as novel biomarkers for Rett syndrome.PloS one · 2019Article
- Enriched expression of genes associated with autism spectrum disorders in human inhibitory neurons.Translational psychiatry · 2018Article
- Adult Neural Stem Cell Multipotency and Differentiation Are Directed by the Methyl-CpG-Binding Protein MBD1.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2017Article
- Higher O-GlcNAc Levels Are Associated with Defects in Progenitor Proliferation and Premature Neuronal Differentiation duringFrontiers in cellular neuroscience · 2017Article
- CRISPR/Cas9-mediated heterozygous knockout of the autism gene CHD8 and characterization of its transcriptional networks in cerebral organoids derived from iPS cells.Molecular autism · 2017Article
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 2 countries.
Funding
Abstract
Genes implicated in neurodevelopmental disorders (NDDs) important in cognition and behavior may have convergent function and several cellular pathways have been implicated, including protein translational control, chromatin modification, and synapse assembly and maintenance. Here, we test the convergent effects of methyl-CpG binding domain 5 (MBD5) and special AT-rich binding protein 2 (SATB2) reduced dosage in human neural stem cells (NSCs), two genes implicated in 2q23.1 and 2q33.1 deletion syndromes, respectively, to develop a generalized model for NDDs. We used short hairpin RNA stably incorporated into healthy neural stem cells to supress MBD5 and SATB2 expression, and massively parallel RNA sequencing, DNA methylation sequencing and microRNA arrays to test the hypothesis that a primary etiology of NDDs is the disruption of the balance of NSC proliferation and differentiation. We show that reduced dosage of either gene leads to significant overlap of gene-expression patterns, microRNA patterns and DNA methylation states with control NSCs in a differentiating state, suggesting that a unifying feature of 2q23.1 and 2q33.1 deletion syndrome may be a lack of regulation between proliferation and differentiation in NSCs, as we observed previously for TCF4 and EHMT1 suppression following a similar experimental paradigm. We propose a model of NDDs whereby the balance of NSC proliferation and differentiation is affected, but where the molecules that drive this effect are largely specific to disease-causing genetic variation. NDDs are diverse, complex and unique, but the optimal balance of factors that determine when and where neural stem cells differentiate may be a major feature underlying the diverse phenotypic spectrum of NDDs.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.